6-162591579-G-T

Variant names:

• chr6-162591579-G-T
• rs2803059
• NM_004562.3:c.7+136083C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004562.3(PRKN):​c.7+136083C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,818 control chromosomes in the GnomAD database, including 11,094 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11094 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343
• Publications: 4 publications found

Genes affected

PRKN (HGNC:8607): (parkin RBR E3 ubiquitin protein ligase) The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]

PRKN Gene-Disease associations (from GenCC):

• autosomal recessive juvenile Parkinson disease 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
• Parkinson disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.7+136083C>A		intron_variant	Intron 1 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.7+136083C>A		intron_variant	Intron 1 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55243 AN: 151700 Hom.: 11081 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.0345

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55270 AN: 151818 Hom.: 11094 Cov.: 32 AF XY: 0.358 AC XY: 26568 AN XY: 74194

African (AFR) AF: 0.260 AC: 10756 AN: 41404

American (AMR) AF: 0.275 AC: 4203 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1671 AN: 3464

East Asian (EAS) AF: 0.0344 AC: 178 AN: 5174

South Asian (SAS) AF: 0.342 AC: 1642 AN: 4804

European-Finnish (FIN) AF: 0.445 AC: 4674 AN: 10510

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30964 AN: 67896

Other (OTH) AF: 0.375 AC: 789 AN: 2104

Alfa AF: 0.401 Hom.: 3091

Bravo AF: 0.346

Asia WGS AF: 0.215 AC: 750 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2803059; hg19: chr6-163012611; COSMIC: COSV58269329;